OBJECTIVE: To investigate the inhibitory effect of gonadotropin-releasing hormone II(GnRHII) and gonadotropin-releasing hormone I agonist (GnRH Ia) on the proliferation of endometrial stromal cells in vitro from endometriosis patients. METHODS: Different concentrations of GnRHII or GnRH Ia were added into the cultured endometrial stromal cells in vitro to detect the cell proliferation inhibition by MTT test. RESULTS: The inhibitory rate of GnRHII or GnRH Ia on eutopic and ectopic endometrial stromal cells in vitro was both dose- and time-dependent (P<0.05). Effect of GnRHII or GnRH Ia on the inhibitory rate of ectopic endometrial stromal cells was significantly higher than that of eutopic (P<0.05). GnRH II had a higher inhibitory rate on the endometrial stromal cells in vitro than did GnRH Ia (P<0.05). CONCLUSION GnRHII has more antiproliferative effect on endometrial stromal cells than GnRH Ia in vitro, especially on ectopic endometrial stromal cells, suggesting that GnRHII may be more effective than GnRH Ia on endometriosis.
Adult ; Cell Proliferation ; drug effects ; Cells, Cultured ; Endometriosis ; pathology ; Endometrium ; metabolism ; pathology ; Female ; Gonadotropin-Releasing Hormone ; agonists ; analogs & derivatives ; pharmacology ; Humans ; Middle Aged ; Stromal Cells ; pathology ; Young Adult

OBJECTIVETo investigate the effects of progesterone and progestin on the expressions of regulated on activation, normal T cell expressed and secreted (RANTES) in eutopic endometrium from patients with endometriosis.

METHODSWe collected the samples of endometrium from patients with endometriosis before operation or after insertion of levenorgestrel releasing intrauterine system (LNG-IUS), administration of oral medroxyprogesterone (MPA), or injection of gonadotrophic hormone releasing hormone agonist (GnRHa). Reverse transcription-polymerase chain raction was used to assay the expression of RANTES mRNA. On the other hand, progesterone (Po) and tumor necrosis factor-alpha (TNFalpha) of different concentrations and different manners were used to treat cultured cells in vitro. RANTES secretion was evaluated in the culture medium using ELISA. In order to evaluate the effect of Po on the secretion of RANTES under stimulation of TNFalpha, the cells were cultured in medium containing 100 U/ml TNFalpha and Po of different concentrations for 24 hours. After the pretreatment of Po for 48 hours at different concentrations, TNFalpha (100 U/ml, 16 h) was added to observe whether Po inhibits RANTES or not.

RESULTSThe expression of RANTES mRNA in eutopic endometrium of patients with endometriosis was significantly higher than in control group (28.0 +/- 9.0 vs. 22.0 +/- 5.6, P < 0.05). Following the exposures to LNG-IUS (24.0 +/- 4.2 vs. 25.9 +/- 4.2, P > 0.05) or GnRHa (23.0 +/- 12.9 vs. 26.9 +/- 5.2, P > 0.05), the expression of RANTES mRNA had no change. MPA significantly increased the expression of RANTES mRNA (42.6 +/- 3.1 vs. 24.3 +/- 5.7, P < 0.05). Po itself had no significant effect on the secretion of RANTES. Stimulated by Po and TNFalpha at the same time, the secretion of RANTES significantly increased. After pretreatment with Po for 48 hours, the reaction of RANTES to the stimulating effect of TNFalpha was down-regulated.

CONCLUSIONThe eutopic endometrium of patients with endometriosis has high chemotactic activity. It may be feasible to prevent and treat endometriosis with progestins.

Cells, Cultured ; Chemokine CCL5 ; biosynthesis ; Endometriosis ; drug therapy ; metabolism ; Endometrium ; drug effects ; metabolism ; Female ; Gonadotropin-Releasing Hormone ; agonists ; Humans ; Intrauterine Devices, Medicated ; Levonorgestrel ; therapeutic use ; Medroxyprogesterone ; therapeutic use ; Progesterone ; pharmacology ; therapeutic use ; Progestins ; therapeutic use ; Transforming Growth Factor alpha ; pharmacology

No abstract available.
*Castration ; Cyproterone Acetate/adverse effects/therapeutic use ; Gonadotropin-Releasing Hormone/agonists/metabolism ; Humans ; Male ; Medroxyprogesterone Acetate/adverse effects/therapeutic use ; Physicians/*psychology ; Prostatic Neoplasms/etiology ; Psychotherapy ; Sex Offenses/*prevention & control

A 65-yr-old woman presented 17 yr status post-hysterectomy with bilateral ovarian salpingo-oophorectomy, attributable to ovarian cancer. She was admitted to our hospital, with multiple cystic liver masses and multiple large seeded masses in her abdomen and pelvic cavity. Histological examination of the pelvic masses demonstrated granulosa cell tumors. After two courses of systemic combination chemotherapy, with paclitaxel and carboplatin, the masses in the abdomen and pelvic cavity increased, and debulking surgery also failed because of peritoneal dissemination with severe adhesion. Finally, she underwent palliative radiotherapy for only the pelvic masses obstructing the urinary and GI tracts, and monthly hormonal therapy with a gonadotrophin-releasing hormone agonist; leuprorelin 3.75 mg IM. Subsequently, multiple masses beyond the range of the radiation as well as those within the radiotherapy field partially decreased. This partial response had been maintained for more than 8 months as of the last follow-up visit. Owing to its long and indolent course and the low metabolic rate of the tumors, advanced or recurrent granulosa cell tumor (GCT) requires treatment options beyond chemotherapy, surgery, and radiotherapy. Hormonal agents may provide another treatment option for advanced or recurrent GCT in those who are not candidates for surgery, chemotherapy, or radiotherapy.
Aged ; Antineoplastic Agents, Hormonal/*therapeutic use ; Female ; Gonadotropin-Releasing Hormone/*agonists/metabolism ; Granulosa Cell Tumor/diagnosis/*drug therapy/radiography ; Humans ; Leuprolide/*therapeutic use ; Ovarian Neoplasms/diagnosis/*drug therapy/radiography ; Recurrence

OBJECTIVETo study the effect of gonadotroph-releasing hormone (GnRH) agonist (GnRH-a) and GnRH antagonist (GnRH-ant) against cyclophosphamide (CTX)-induced gonadotoxicity in female rats.

METHODSThirty-six female SD rats were divided randomly into 6 groups to receive treatment with normal saline (NS), CTX, GnRH-a+NS, GnRH-a+CTX, GnRH-ant+NS, GnRH-ant+CTX, respectively. The rats were sacrificed between the first and second week after termination of the medication to compare the weight of the ovaries, the number of the primordial follicles and the follicle growth. The expressions of bcl-2 and bax mRNA in the ovaries were examined using RT-PCR.

RESULTSThe number of the primordial follicles was significantly greater and that of the growing follicles significantly lower in GnRH-a+NS and GnRH-a+CTX groups than in the GnRH-ant+CTX and CTX groups (P<0.05). The rats in GnRH-a+NS and GnRH-a+CTX groups had the lowest ovarian weight among 6 the groups (P<0.05). The bcl-2 mRNA level in the GnRH-ant+NS group was significantly higher than that in the other groups (P<0.05). The Bax mRNA in the GnRH-a+NS and GnRH-a+CTX groups was significantly higher than that in the NS group (P<0.05), but close to that in the CTX group (P>0.05); bax mRNA expression in the GnRH-ant+NS group was significantly lower than that in the NS group (P<0.05), but in GnRH-ant+CTX group, its expression was close to that in the NS group (P>0.05).

CONCLUSIONSIn female rats exposed to CTX, the GnRH analogs provides ovarian protection against CTX-induced gonadotoxicity by regulating the expression of the Bax mRNA in the ovary. GnRH-a may decrease the sensitivity of the follicles to CTX-induced gonadotoxicity by promoting follicle apoptosis and inhibiting follicle proliferation, and GnRH-ant increases the sensitivity to the CTX through a reverse effect on the follicles.

Animals ; Apoptosis ; drug effects ; Cyclophosphamide ; antagonists & inhibitors ; pharmacology ; Female ; Gonadotropin-Releasing Hormone ; agonists ; antagonists & inhibitors ; Ovary ; drug effects ; metabolism ; pathology ; Proto-Oncogene Proteins c-bcl-2 ; genetics ; metabolism ; RNA, Messenger ; genetics ; metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; bcl-2-Associated X Protein ; genetics ; metabolism

The therapeutic effects and side effects of androgen deprivation therapy (ADT), which is a main treatment method for metastatic prostate cancer, are well known, but the metabolic effects have only recently been studied. This review describes the effects of ADT on body habitus, insulin resistance, lipid profiles, diabetes, metabolic syndrome, and cardiovascular morbidity and mortality. The review was done by using KoreaMed and PubMed to search the medical literature related to prostate cancer, ADT, body habitus, lipid profile, diabetes, insulin resistance, metabolic syndrome, and cardiovascular disease. ADT increases fat mass and decreases lean body mass. Fat mostly accumulates in the subcutaneous area. ADT increases total cholesterol, triglycerides, and high-density lipoprotein, as well as the risk for insulin resistance and diabetes. ADT also increases the risk for cardiovascular events, but insufficient evidence is available for a correlation with mortality. ADT changes body habitus and lipid profiles and has different characteristics than those of classic metabolic syndrome, but it is related to insulin resistance and diabetes. ADT increases the risk for cardiovascular events. No consistent guidelines have been proposed for treating the metabolic effects of ADT, but the generally recommended treatment methods for lowering the risk of diabetes and cardiovascular disease should be fully understood. Additional studies are necessary.
Androgen Antagonists/*adverse effects/therapeutic use ; Body Composition/drug effects ; Cardiovascular Diseases/metabolism/mortality ; Cholesterol/chemistry ; Diabetes Mellitus/epidemiology/metabolism ; Gonadotropin-Releasing Hormone/*agonists ; Humans ; Insulin Resistance ; Lipids/blood ; Lipoproteins, HDL/blood ; Male ; Metabolic Syndrome X/epidemiology/metabolism ; Prostatic Neoplasms/*drug therapy ; Risk Factors ; Triglycerides/chemistry

PURPOSE: Docetaxel-based chemotherapy (DTX) improves overall survival (OS) of men with metastatic castration-resistant prostate cancer (mCRPC). Considering the potential existence of androgen receptors that remain active at this stage, we aimed to assess the impact of the combined use of androgen deprivation therapy (ADT) with DTX for mCRPC. MATERIALS AND METHODS: We performed a single-institutional retrospective analysis of patients with mCRPC who received either DTX alone (DTX group, n=21) or concurrent DTX and ADT (DTX+ADT group, n=26) between August 2006 and February 2014. All patients received DTX doses of 75 mg/m2 every three weeks for at least three cycles. In the DTX+ADT group, all patients used luteinizing hormone releasing hormone agonist continuously as a concurrent ADT. RESULTS: The median follow-up period was 24.0 months (interquartile range 12.0-37.0) for the entire cohort. The median radiographic progression-free survival (rPFS) was 9.0 months and 6.0 months in the DTX+ADT and DTX groups, respectively (log-rank p=0.036). On multivariable Cox regression analysis, concurrent administration of ADT was the only significant predictor of rPFS [hazard ratio (HR)=0.525, 95% confidence intervals (CI) 0.284-0.970, p=0.040]. The median OS was 42.0 and 38.0 months in the DTX+ADT and DTX groups, respectively (log-rank p=0.796). On multivariable analysis, hemoglobin level at the time of DTX initiation was associated with OS (HR=0.532, 95% CI 0.381-0.744, p<0.001). CONCLUSION: In chemotherapy-naive patients with mCRPC, the combined use of ADT with DTX improved rPFS. Our result suggests that the concurrent administration of ADT and DTX is superior to DTX alone.
Adenocarcinoma/blood/*drug therapy/secondary ; Aged ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Disease-Free Survival ; Gonadotropin-Releasing Hormone/administration & dosage/agonists ; Hemoglobins/metabolism ; Humans ; Male ; Middle Aged ; Prostatic Neoplasms, Castration-Resistant/blood/*drug therapy/pathology ; Retrospective Studies ; Survival Rate ; Taxoids/administration & dosage

AIMTo study the effect and mechanism of gonadotrophin-releasing hormone (GnRH) on murine Leydig cell steroidogenesis.

METHODSPurified murine Leydig cells were treated with GnRH-I and -II agonists, and testosterone production and steroidogenic enzyme expressions were determined.

RESULTSGnRH-I and -II agonists significantly stimulated murine Leydig cell steroidogenesis 60%-80% in a dose- and time-dependent manner (P < 0.05). The mRNA expressions of steroidogenic acute regulatory (StAR) protein, P450scc, 3beta-hydroxysteroid dehydrogenase (HSD), but not 17alpha-hydroxylase or 17beta-HSD, were significantly stimulated by both GnRH agonists with a 1.5- to 3-fold increase (P < 0.05). However, only 3beta-HSD protein expression was induced by both GnRH agonists, with a 1.6- to 2-fold increase (P < 0.05).

CONCLUSIONGnRH directly stimulated murine Leydig cell steroidogenesis by activating 3b-HSD enzyme expression.

3-Hydroxysteroid Dehydrogenases ; biosynthesis ; genetics ; Animals ; Blotting, Western ; Cell Separation ; Cells, Cultured ; Cholesterol Side-Chain Cleavage Enzyme ; biosynthesis ; Dose-Response Relationship, Drug ; Gonadotropin-Releasing Hormone ; agonists ; pharmacology ; Leydig Cells ; drug effects ; metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Phosphoproteins ; biosynthesis ; genetics ; RNA ; biosynthesis ; isolation & purification ; Reverse Transcriptase Polymerase Chain Reaction ; Sexual Maturation ; physiology ; Steroids ; biosynthesis ; Testosterone ; biosynthesis